The present invention relates to an adhesive for biological tissue. More particularly, the present invention relates to an adhesive for biological tissue containing a glue agent and a cross-linking agent, such that the glue agent contains a recombinant human plasma protein as a main component, and that the cross-linking agent contains a bifunctional or multifunctional aldehyde an a main component, the adhesive providing excellent hemostatic and adhesion properties and being biologically absorbable and highly safe. 2. Description of the Related Art
Conventionally, various adhesives have been proposed as adhesives for biological tissue. Among others, cyanoacrylate type adhesives (e.g., Aronalpha A from ToaGosei Industry Co., Ltd. and Biobond from Yoshitomi Pharmaceutical Industries, Ltd.), fibrin glues (e.g., Tisseel from Nippon Zoki K.K., Beriplast from Hoechst, and Bolheal from The Chemo-Sero-Therapeutic Research Institute), and gelatin-resorcin-(bifunctional or multifunctional) aldehyde type adhesives (e.g., Cardial GRP Glue from Cardial (France)) are used in actual clinical applications. (See for example, Journal of Biomedical Materials Research, vol. 31, 157-166 (1996).)
The features of conventional tissue adhesives which are used for clinical purposes will now be summarized. First, cyanoacrylate type adhesives provide good adhesion speed and adhesion strength. However, this type of adhesives have significant problems in that flexibility is lost from the adhesion surface obtained by using this type of adhesives, and substances which may pose safety hazards might be produced through in vivo-degradation. Fibrin glues are considered free from safety concerns associated with in vivo-degradation products since they are of biological origin. However, fibrin glues have problems in that they provide somewhat lower adhesion strength. Also, the possibilities of viral infection associated with the use of fibrin glues are non-negligible. Gelatin-resorcin-aldehyde type adhesives provide good adhesion strength. However, this type of adhesive also has problems in that some products employ highly-toxic formaldehyde as an aldehyde, and that gelatin is not entirely free from prion infection possibilities.
Adhesives containing a plasma protein obtained from blood, e.g., serum albumin, and a bifunctional or multifunctional aldehyde have been proposed and are known to provide good adhesion strength (See, for example, PCT Publication WO04/01508; this publication is incorporated herein by reference). Some of these adhesives are used for clinical purposes in Europe. However, this type of adhesives are not entirely free from safety concerns because there are possibilities of infection with viruses from human or animal blood products or derivatives. Therefore, those who are engaged in clinical practice are awaiting the development of an adhesive for biological tissue which provides good adhesion strength and yet is highly safe.